Strategy for Increasing Drug Solubility and Efficacy through Covalent Attachment to Polyvalent DNA-Nanoparticle Conjugates*

Abstract

An approach has been developed for increasing Paclitaxel solubility and effectiveness by covalent attachment to gold nanoparticles via DNA linkers. The resulting conjugates are highly soluble in aqueous buffer, exhibiting greater than a 50-fold increase in solubility over the unconjugated drug. DNA linkers are labeled with a fluorophore, which affords a convenient means of visualizing resultant conjugates within cells. One emerging and important class of nanomaterials, polyvalent DNA-functionalized gold nanoparticles, has been studied and utilized extensively in the fields of biodiagnostics, gene regulation, and nanomedicine. Covalently attaching hydrophobic Paclitaxel onto gold nanoparticles via a DNA spacer resulted in significantly enhanced hydrophilicity and stability as compared to free Paclitaxel alone. Attachment to DNA-nanoparticle conjugates may become a general strategy for solubilizing and enhancing a wide variety of therapeutic agents in aqueous media. Covalently attaching hydrophobic Paclitaxel onto gold nanoparticles via a DNA spacer resulted in significantly enhanced hydrophilicity and stability as compared to free Paclitaxel alone.